Citations

Purpose: A variety of care pathways are offered to females with chronic pelvic pain (CPP) and pelvic floor myofascial pain (PFMP), which may affect treatment outcomes. This study aims to compare care pathways and describe health care utilization and characteristics of patients with CPP and PFMP referred for physical therapy (PT) at a tertiary care center. Methods: A retrospective cohort analysis was conducted on females with CPP and PFMP referred for PT. Patients received PT, medication management, injection therapy, or a combination of treatments. We collected data on health care utilization, comorbidities of interest, and patient-reported outcome measures (PROMs). Wilcoxon rank-sum tests were used to compare patients with pre- and posttreatment PROM scores. Results: A total of 1172 patients were referred for PT treatment, but 19.5% (n = 229) did not attend any PT sessions, and only 18% (n = 211) of patients attended the recommended number of PT sessions. Comorbid urinary (48.5%, n = 569) and bowel dysfunction (43%, n = 512) were prevalent. Patients consulted with multiple providers. Most patients (57.1%, n = 669) utilized opioid medications. Less than 20% completed both pre-and posttreatment PROMs. Discussion: Care pathways vary widely for the treatment of PFMP. Low adherence to PT and a trend toward greater than 5 subspecialty appointments indicating higher health care utilization reflect the range of inconsistent patient experience likely affecting outcomes. Outcomes of care are uncharted territory. Optimal care pathways for CPP and PFMP need to be established, along with further investigation of PROMs, to determine which treatments result in effective outcomes that matter to patients.

ABSTRACT Objective Identifying risk factors enables stratification of patients’ susceptibility to inflammatory arthritis immune-related adverse events (IA-irAE). This retrospective study examines whether preexisting osteoarthritis (OA) increases the likelihood of de novo IA in patients treated with immune checkpoint inhibitors (ICIs). Methods The prevalence of OA among ICI–treated patients who developed IA-irAE, those who developed other types of irAEs but not IA (non-IA irAE), and those who did not develop any irAEs (non-irAE) were compared. Electronic medical records were reviewed to extract demographic, clinical and laboratory data. Group comparisons and logistic regression analyses were performed. Results 181 de novo IA-irAE patients, 140 non-IA irAE patients and 170 non-irAE patients were included. The prevalence of OA was significantly higher in the IA-irAE group (69%) than the non-IA irAE group (48%) and the non-irAE group (48%) (both p < 0.001). The IA-irAE group demonstrated a higher frequency of multisite OA, with predominant hand involvement (62%) than the non-IA irAE with OA group (13%) and the non-irAE with OA group (13%) (both p < 0.001). A family history of autoimmune disease (AID) (OR 2.03, 95% CI 1.02–4.05), preexisting OA (OR 2.88, 95% CI 1.85–4.52) and melanoma (OR 2.63, 95% CI 1.56–4.47) were identified as risk factors for the development of IA-irAE. Conclusions OA was more prevalent among ICI-treated patients developing IA-irAE than those who did not. Hand OA was the most common OA pattern in IA-irAE patients. Preexisting OA, melanoma and a family history of AID were risk factors for IA-irAE.

Importance Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive and potentially life-threatening infection that predominantly affects immunocompromised patients. Recent advances in diagnostic imaging, antifungal therapy, and surgical techniques may have altered its incidence, morbidity, and mortality. Objective To evaluate temporal trends in the pooled proportion, morbidity, and mortality of AIFRS in immunocompromised patients and assess the association of diagnostic and therapeutic advances. Data Sources Systematic searches of Ovid MEDLINE, Ovid Embase, PubMed, Scopus, Web of Science, Cochrane, and Google Scholar from 1977 through October 20, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study Selection Prospective, retrospective, and cross-sectional studies and case series reporting pooled proportion, morbidity, or mortality of AIFRS in immunocompromised patients were included. Non-English articles, reviews, editorials, and studies with fewer than 10 patients were excluded. Data Extraction and Synthesis Two independent reviewers extracted data using standardized templates; disagreements were resolved by consensus. Risk of bias was assessed using the Newcastle-Ottawa Scale and Murad tool for case series. Random-effects meta-analysis generated pooled proportion, morbidity, and mortality rates with 95% CIs. Heterogeneity was quantified using I 2 statistics. Meta-regression and sensitivity analyses evaluated temporal trends and study-level effects. Main Outcomes and Measures Pooled proportion, morbidity, and mortality rates of AIFRS stratified by publication period (1983-2012 vs 2013-2025). Results A total of 205 studies comprising 48 437 immunocompromised patients (median [range] age, 49.4 [5.2-68.8] years), including 10 311 (21.3%) with AIFRS, were analyzed. The pooled proportion was 11.8% (95% CI, 7.9%-17.2%), rising to 16.6% (95% CI, 8.7%-29.2%) in studies from 2013 to 2025. Overall mortality was 31.2% (95% CI, 28.3%-34.3%), declining from 41.9% (95% CI, 35.0%-49.1%) before 2013 to 28.2% (95% CI, 25.1%-31.4%) after 2013. Morbidity was 37.0% (95% CI, 32.9%-41.4%), with similar rates across periods (39.3% before 2013 vs 36.4% after 2013). The most common complications were vision loss, exophthalmos/proptosis, and orbital exenteration. Conclusions and Relevance This systematic review and meta-analysis suggests that the pooled proportion of AIFRS among immunocompromised patients has increased while mortality has declined, reflecting advances in diagnostic and therapeutic approaches. Early detection and aggressive management remain critical to improving outcomes.

Abstract Background JAK inhibitors (JAKi) are small molecules that cross the placenta from early pregnancy.1 Evidence on the safety of in utero JAKi exposure remains limited, particularly regarding pregnancy outcomes, infant infections, vaccine responses, and early development.2, 3 Methods We conducted a multicenter retrospective study within the ECCO CONFER network, including pregnant women with inflammatory bowel disease (IBD) exposed to tofacitinib (TOFA), upadacitinib (UPA), or filgotinib (FILGO). Data were collected from 22 centers across 16 countries and included maternal characteristics, disease activity, medication patterns, and pregnancy and infant outcomes. Results Among 55 JAKi exposed pregnancies, 21 (38.2%) were unplanned and 30 (54.6%) had active disease. Nine women (16.4%) initiated JAKi during pregnancy. Overall, 38 (69.1%) received TOFA, 15 (27.3%) UPA, and 2 (3.6%) FILGO; 39 (70.9%) continued treatment throughout pregnancy. JAKi discontinuation in 1st-2nd trimester led to disease activity in 9/16 cases (56.3%). Maternal complication risk was low: no DVT or (pre) eclampsia occurred; three cases of premature rupture of membranes (GA 34–37) and four required hospitalizations due to infection or other complications. A total of 10 abortions occurred - five spontaneous (9.1%) and five induced (9.1%), including three due to concern about JAKi exposure. Among 45 live births, two infants (3.6%) were preterm, four (7.3%) small for gestational age, and two (3.6%) had Apgar &lt;7 at 5 minutes. No congenital abnormalities were reported. Infant follow-up findings are summarized in Table 1. One-third of breastfeeding women continued JAKi postpartum. A high adherence rate to the national immunization schedule was seen. Eight (19.5%) received the live BCG-vaccine within the first 30 days of life. No adverse events followed live or inactivated vaccines, and no malignancies were observed. Conclusion In this global cohort of JAKi-exposed pregnancies in women with IBD, maternal complication rates were low, and no increased risk of adverse outcomes among live births was identified. While disease activity was common, particularly following discontinuation of JAKi, infant outcomes - including development, infection risk, and vaccine response - were reassuring. These findings provide important preliminary safety data to inform decision-making regarding JAKi use in pregnancy, though prospective studies are needed to confirm long-term safety. References: 1.Fein KC, Arral ML, Kim JS, et al. Placental drug transport and fetal exposure during pregnancy is determined by drug molecular size, chemistry, and conformation. J Control Release 2023;361:29–39. 2.Torres J, Chaparro M, Julsgaard M, et al. European Crohn’s and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023;17:1–27. 3.Mahadevan U, Seow CH, Barnes EL, et al. Global Consensus Statement on the Management of Pregnancy in Inflammatory Bowel Disease. J Crohns Colitis 2025;epub ahead of print. Conflict of interest: Julsgaard, Mette: No conflict of interest Baunwall, Simon MD: No conflict of interest Seow, Cynthia: No conflict of interest Duricova, Dana: No conflict of interest Kane, Sunanda: No conflict of interest Zacharias, Neha: No conflict of interest Leong, Rupert: No conflict of interest Cremer, Anneline: No conflict of interest Kok, Klaartje: No conflict of interest Kagramanova, Anna Valeryevna: No conflict of interest Pipek, Barbora: No conflict of interest Candido, Kristina: No conflict of interest Cooney, Rachel: No conflict of interest Filip, Rafal: No conflict of interest Kiudelis, Vytautas: No conflict of interest Konečný, Michal: No conflict of interest Paramsothy, Sudarshan: No conflict of interest Pugliese, Daniela: No conflict of interest Oliveira Santana Silva, Genoile: Honoraria - Abbvie, Johnson & Johnson, Ferring, Takeda. Research - Abivax, Takeda, Johnson & Johnson, Roche, Sanofi, Polpharma. Advisory board - Abbvie, Johnson & Johnson, MSD. Savarino, Edoardo Vincenzo: No conflict of interest Smolovic, Brigita: No conflict of interest Vieujean, Sophie: No conflict of interest Wei, Shu Chen: No conflict of interest Mahadevan-Velayos, Uma: No conflict of interest

Objective The objective of this study was to investigate the association between dual seropositive, single seropositive, and seronegative rheumatoid arthritis (RA) with radiographic erosions, disease flares, and death. Methods We performed a retrospective, population‐based study of residents in Southern Minnesota with incident RA who fulfilled criteria for RA in 2003 to 2019. Radiographic erosions and flares were evaluated within one year of incident RA. All‐cause mortality was obtained from medical records and death certificates. Cox models adjusted for age, sex, smoking status, year of incident RA, and comorbidities were used. Results The study included 1,373 patients with RA. At RA incidence, 37% were dual seropositive, 13% seropositive for anti–cyclic citrullinated protein (anti‐CCP) only, 12% seropositive for rheumatoid factor (RF) only, and 38% seronegative. The highest proportion of radiographic erosions before or within one year of RA incidence was in the dual seropositive (31%) and lowest in those seropositive for anti‐CCP only (13%). Flares occurred in 69% of the dual seropositive and 51% of the seropositive for anti‐CCP only within the first year of RA incidence. Those seropositive for RF only had over a two‐fold increase in mortality rates compared with the seronegatives (adjusted hazard ratio [aHR] 2.18, 95% confidence interval [CI] 1.47–3.24). In contrast, the dual seropositives had only a >50% increase in mortality rates (aHR 1.66, 95% CI 1.21–2.28), and those seropositive only for anti‐CCP had a >30% increase in mortality rates (aHR 1.32, 95% CI 0.83–2.11). Conclusion Patients with RA seropositive for RF only have an increase in mortality rates compared with patients who are dual seronegative. RF positivity could be an indicator of inflammation that requires pharmacologic treatment to decrease mortality rates.

Abstract Background Measurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort. Methods Lithium-heparin plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 IFCC guidance. Uniform and sex-specific 99th percentile URLs and nonparametric 95% CIs were determined in plasma and serum separately and combined. Results The final study population comprised 4147 participants (52.5% female) with a median (25th–75th percentiles) age of 48.0 (33.0–59.0) years; 45.8%, 47.9%, 5.2%, and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n = 8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16–23) ng/L for females and 32 (28–35) ng/L for males; the uniform 99th percentile URL was 27 (24–31) ng/L. URLs were comparable in plasma and serum samples. Conclusions This study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used in a large, global, healthy reference population.

Abstract Background Tau phosphorylation and aggregation are hallmark features of Alzheimer's disease pathology(AD). Previous studies have shown that plasma phosphorylated tau( p ‐tau) at threonine 217 can detect AD‐related tau tangle pathology. However, the head‐to‐head association between p ‐tau217 and different tau PET tracers remains unexplored. Here, we conducted a head‐to‐head comparison of the association between plasma p ‐tau217 and four distinct tau PET tracers[MK6240, Flortaucipir(FTP), PI2620, RO948]. Method We studied 338 individuals across the AD continuum from the HEAD study[190 cognitively unimpaired elderly(CU), 109 with mild cognitive impairment(MCI), and 39 with dementia] with available FTP, MK6240, and plasma p ‐tau217 measured by ALZpath assay. A subset of 64 individuals(28 CU, 25 MCI, and 11 dementia) also had PI2620 and RO948, and p ‐tau217 measured by Lumipulse. The strength of the association was determined using t‐value maps from regression models testing the association between each tau PET tracer and plasma p ‐tau217, and the extent was measured by the percentage of significant voxels(t‐value>3.2). R‐square metric was used to determine how much of the variance in tau PET tracer estimates was explained by plasma p ‐tau217 concentrations. Associations between p ‐tau217 with tau PET were evaluated using the Spearman test. Result We found that in CU, both the extent and magnitude of the association with plasma p ‐tau217 were higher for MK6240 compared to FTP (Figure 1A‐D). Plasma p ‐tau217 explained a greater proportion of the variance in MK6240 than in FTP (Figure 1E‐F). In CI, the extent and magnitude of the association were similar for MK6240 and FTP. Additionally, plasma p ‐tau217 explained a similar proportion of the variance in MK6240 and FTP. Using the subset of individuals who had all tau tracers, MK6240 showed a slightly higher extent of association with p ‐tau217, followed by FTP, PI2620, and RO948 (Figure 2A‐B). The magnitude of association was stronger for MK6240, followed by PI2620, RO948, and FTP (Figure 2C‐D). Plasma p ‐tau217 explained a greater proportion of the variance in MK6240, followed by FTP, RO948, and PI2620 (Figure 2E‐F). We compared the associations between different p ‐tau217 assays, and both assays presented similar associations with all tau PET tracers (Figure 3). Conclusion In summary, our results indicate that the four tau PET tracers exhibit robust associations with plasma p ‐tau217 in similar topographical regions.

Abstract Background Dementia with Lewy Bodies (DLB) has been overlooked or misdiagnosed as Alzheimer's disease (AD) dementia due to its frequent concomitant AD pathology with Lewy Body Disease (LBD) pathology. Although autopsy confirmation has been the gold standard for the precise diagnosis of DLB, time‐course 123 I‐FP‐CIT SPECT (DaT‐SPECT) findings in autopsy‐confirmed DLB are not well characterized. We previously reported that the DaTQUANT z‐score of the more affected side of the putamen has the best discriminatory power in detecting LBD pathology and nigrostriatal degeneration in dementia patients and demonstrated z‐score of −1 as the cutoff value. We sought to examine how DaT‐SPECT findings change over time in autopsy confirmed LBD patients in preparation for its use in LBD targeted clinical trials. Method Eight autopsy confirmed neocortical or limbic LBD patients who underwent two or more DaT‐SPECT were included. Nigrostriatal dopamine transporter (DaT) binding and age‐adjusted z‐scores were analyzed using the DaTQUANT 2.0 software (GE Healthcare). Result Six patients (75%) were male. The patients had 2.5±0.7 longitudinal DaT‐SPECT scans. Clinical diagnosis at initial scan was: DLB (75%), mild cognitive impairment (MCI) with REM sleep behavior disorder (RBD) (13%), and isolated RBD (iRBD) (13%). Clinical diagnosis at last scan was: DLB (88%) and iRBD (12%). All patients developed dementia during life. Mean age at initial scan/last scan/autopsy were 71.1±7.0/73.4±6.9/75.1±7.3 years old. Time from initial and last scan to autopsy were 4.0±1.9 and 1.8±1.9 years respectively. Seven patients (88%) had neocortical LBD and one (12%) had limbic LBD. Concomitant AD pathology was observed in four patients (two males (33%), two females (100%)). All patients had DaTQUANT putamen z‐score <‐1.0 at their initial scan including in MCI+RBD (‐1.76) and iRBD (‐1.53) patients. In the DLB patients at their initial scans, five (83%) had DaTQUANT putamen z‐score <‐2.0 and one (17%) had z‐score of ‐1.55. All patients (100%) showed DaTQUANT putamen z‐score <‐2.0 at their last scans. Conclusion DaTQUANT using cut‐off putamen z‐score of ‐1 was associated with underlying LBD pathology including at their iRBD and MCI stages. Nigrostriatal DaT binding tends to decline over time with DaTQUANT z‐score <‐2 at their last scans.

Abstract Background We showed that astrocyte reactivity, as measured by plasma GFAP levels, influences Aβ mediated tau PET pathology in cognitively unimpaired (CU) Aβ‐positive individuals. However, the link between GFAP and tau PET in individuals without detectable Aβ pathology remains elusive. The aim of the current study is to investigate the association between plasma GFAP and tau PET in CU Aβ PET‐negative individuals. Method We studied 147 CU Aβ PET‐negative participants from the HEAD cohort with plasma GFAP and p ‐tau217, as well as tau PET Flortaucipir and MK6240 data. Aβ positivity was determined by Aβ PET visual reading and Centiloid 12. Voxel‐wise linear regression models adjusted for age and sex tested the association of plasma GFAP and p ‐tau217 with tau PET. Further, the associations of plasma GFAP with peak tau PET SUVR values extracted from voxel‐wise association were fitted with a linear regression model adjusted for age and sex. Result Voxel‐wise analysis showed that plasma GFAP levels, but not plasma p ‐tau217 levels, were associated with tau PET in the medial temporal lobe (e.g., amygdala, entorhinal cortex, hippocampus) predominantly for Flortaucipir tau PET [Figure 1A, B, C, D]. The association between plasma p ‐tau217 and tau PET was weak in Aβ‐negative individuals. These results were similar when Aβ positivity was defined based on Centiloid 12. Furthermore, plasma GFAP and peak tau PET SUVR of Flortaucipir showed stronger association than that of MK6240 [Flortaucipir: β=0.4017, p <0.0001; MK6240: β=0.194, p = 0.0424; Figure 2A, B]. Conclusion We found an association between GFAP levels and tau PET uptake in individuals not expected to exhibit high levels of tau tangle‐related tracer uptake. Further analysis will be designed to elucidate the underpinning of this association, which could represent low levels of tau pathology, astrogliosis, or other factors.